Duloxetine CAS 116539-59-4
Introduction：Basic information about Duloxetine CAS 116539-59-4, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Duloxetine Basic information
| Product Name: | Duloxetine |
| Synonyms: | DULOXETINE;DULOXETINE-D3;(S)-DULOXETINE;DULOXETIN;(3S)-N-methyl-3-naphthalen-1-yloxy-3-thiophen-2-yl-propan-1-amine;N-Methyl-gama-(1-naphthalenyloxy)-2-thiophenepropanamine;DULOXETINE HCI;Duloxetine & Intermediates |
| CAS: | 116539-59-4 |
| MF: | C18H19NOS |
| MW: | 297.41 |
| EINECS: | 601-438-0 |
| Product Categories: | API;ACTIVE PHARMACEUTICAL INGREDIENTS |
| Mol File: | 116539-59-4.mol |
Duloxetine Chemical Properties
| Boiling point | 466.2±40.0 °C(Predicted) |
| density | 1.158±0.06 g/cm3(Predicted) |
| storage temp. | Store at -20°C |
| solubility | Soluble in DMSO |
| form | Oil |
| pka | 10.02±0.10(Predicted) |
| color | Light brown to yellow |
| BCS Class | 2 |
| InChI | InChI=1/C18H19NOS.ClH/c1-19-12-11-17(18-10-5-13-21-18)20-16-9-4-7-14-6-2-3-8-15(14)16;/h2-10,13,17,19H,11-12H2,1H3;1H/t17-;/s3 |
| InChIKey | BFFSMCNJSOPUAY-VOPAOICTNA-N |
| SMILES | C1(=CC=CS1)[C@H](CCNC)OC1=CC=CC2=CC=CC=C12.Cl |&1:5,r| |
| EPA Substance Registry System | 2-Thiophenepropanamine, N-methyl-?-(1-naphthalenyloxy)-, (?S)- (116539-59-4) |
Safety Information
| Hazardous Substances Data | 116539-59-4(Hazardous Substances Data) |
| History | Duloxetine is a second-generation antidepressant. Its mechanism of action involves inhibiting the reuptake of serotonin and norepinephrine by neurons, thereby increasing the concentration of these two neurotransmitters in the synaptic cleft, thus improving mood and relieving pain. Initial Approval (2004): Cymbalta was initially approved for the treatment of major depressive disorder (MDD). In the same year, it also received approval for the treatment of diabetic peripheral neuropathy (DPNP), making it a unique drug capable of simultaneously addressing two common and frequently co-occurring conditions: depression and neuropathic pain. Expansion of Indications: Subsequently, Eli Lilly expanded its indications through clinical trials, making it a multi-functional drug. The most significant expansions include generalized anxiety disorder (GAD) (2007), fibromyalgia (2008), and chronic musculoskeletal pain (2010). The approval of these indications secured Cymbalta a significant position in the pain management market, making it one of Eli Lilly's blockbuster drugs. Patent Expiration (2013): In December 2013, Cymbalta's primary patent in the United States expired, a phenomenon known as the "patent cliff." Following the patent expiration, the FDA quickly approved several generic versions (generic name: duloxetine), leading to a significant drop in sales, but also enabling wider use of the drug at a lower price. |
| Uses | Antidepressant. |
| Definition | ChEBI: (S)-duloxetine is a duloxetine. It is an enantiomer of a (R)-duloxetine. |
| Brand name | Cymbalta (Lilly). |
| General Description | Duloxetine (Cymbalta) is a newer antidepressant. It islargely like venlafaxine, which is an SNERI (selective norepinephrinereuptake inhibitor). |
| Pharmacokinetics | Duloxetine appears to be fairly well absorbed after oral doses, with peak plasma levels in 6 to 10 hours andlinear pharmacokinetics. The drug is extensively metabolized in the liver to activemetabolites, with 72% of an oral dose primarily excreted in the urine as conjugated metabolites and up to15% appearing in the feces. N-demethylation to an active metabolite (CYP2D6) and hydroxylation of the naphthyl ring (CYP1A2) at eitherthe 4-, 5-, or 6-positions are the main metabolic pathways for duloxetine. Its metabolites are primarilyexcreted into the urine as glucuronide, sulfate, and O-methylated conjugation products. Themajor metabolites found in plasma also were found in the urine. Preclinical data for 4-hydroxyduloxetinesuggests it has a similar pharmacological profile to duloxetine, with selective inhibition of SERT but lessactivity at the NET. |
| Clinical Use | Duloxetine has been approved for the treatment of depression and diabetic peripheralneuropathic pain. It is another analogue in the line of fluoxetine-based products from Lilly, in which the phenyl and phenoxy groups of fluoxetine have been respectively replaced with the benzene isostere,thiophene, and anaphthyloxy group (previously described under fluoxetine). Duloxetine exhibits dual inhibition with highaffinity for the SERTs and NETs, with a five times preferential inhibition of the SERT. Duloxetineappears to be a more potent in vitro blocker of SERTs and NETs than venlafaxine. In humans, duloxetine hasa low affinity for the other neuroreceptors, suggesting low incidence of unwanted adverse effects. |
| Synthesis | Reaction of 2-acetylthiophenewith paraformaldehyde and dimethylamine inethanol gives 3-(dimethylamino)-1-(2-thienyl)-1-propanone, which is enantioselectively reducedwith a 2:1 complex of (2R,3S)-4-(dimethylamino)-3-methyl-1,2-diphenyl-2-butanoland LiAlH4 in toluene to yield (S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol. Thecondensation of (S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol with 1-fluoronaphthalenecatalyzed by NaH in DMSO affords the correspondingnaphthyl ether (S)-N,N-dimethyl-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propan-1-amine, which is finally monodemethylatedwith 2,2,2-trichloroethyl chloroformate and zincin toluene and treated with oxalic acid . |
| Drug interactions | Potentially hazardous interactions with other drugs Antibacterials: metabolism inhibited by ciprofloxacin - avoid. Anticoagulants: possibly increased risk of bleeding with dabigatran. Other CNS medication: enhanced effect. Antidepressants: avoid with MAOIs, moclobemide, St John’s wort, tryptophan, venlaflaxine, amitriptyline, clomipramine and SSRIs due to increased risk of serotonin syndrome; increased risk of side effects with tricyclic antidepressants; fluvoxamine decreases the clearance of duloxetine by 77% - avoid; possible increased risk of convulsions with vortioxetine. Antimalarials: avoid with artemether/lumefantrine and piperaquine with artenimol. Dapoxetine: avoid concomitant use. Methylthioninium: risk of CNS toxicity - avoid if possible. |
| Metabolism | Duloxetine is extensively metabolised and the metabolites are excreted principally in urine. Both cytochromes P450-2D6 and 1A2 catalyse the formation of the two major metabolites, glucuronide conjugate of 4-hydroxy duloxetine and sulphate conjugate of 5-hydroxy, 6-methoxy duloxetine. Based upon in vitro studies, the circulating metabolites of duloxetine are considered pharmacologically inactive |
Duloxetine Preparation Products And Raw materials
| Raw materials | 1-Fluoronaphthalene |
